Glypican 3 (GPC3) is a member of the family of heparan sulfate proteoglycans present on the surface of cells. It has been suggested that GPC3 may be involved in cell division upon development and in cancer cell growth, but its function is still not well understood.
It has been discovered that a type of antibody that binds to GPC3 inhibits cell growth due to ADCC (antibody-dependent cellular cytotoxicity) activity and CDC (complement-dependent cytotoxicity) activity (WO 2003/00883). Furthermore, because GPC3 is cleaved in the body and secreted into the blood as a soluble form of GPC3, it has been suggested that cancer can be diagnosed using an antibody that can detect the soluble form of GPC3 (WO 2004/022739, WO 2003/100429, WO 2004/018667).
When developing an anticancer agent that utilizes antibody cytotoxic activity, preferably the antibody used will have a high level of ADCC activity. Therefore, an anti-GPC3 antibody with a high level of cytotoxic activity has been demanded.
Modification of antibody sugar chains are known to enhance its ADCC activity. For example, WO 99/54342 discloses that ADCC activity is enhanced by modifying antibody glycosylation. In addition, WO 00/61739 discloses that ADCC activity is regulated by controlling the presence or absence of fucose in antibody sugar chains. WO 02/31140 discloses producing an antibody having sugar chains that do not contain a-1,6 core fucose by producing that antibody in YB2/0 cells. WO 02/79255 discloses an antibody with sugar chains having bisecting GlcNAc. However, an anti-GPC3 antibody with enhanced ADCC activity due to sugar chain modification has not been disclosed so far.